Breakthroughs Blog: NTDs

The Democratic Republic of the Congo has approved the use of a new single-dose oral treatment for sleeping sickness, a potentially fatal disease which is endemic in several countries in Central and West Africa. The approval of Acoziborole Winthrop, codeveloped by the Drugs for Neglected Diseases initiative (DNDi) and Sanofi, follows successful Phase 2 and 3 clinical trials conducted in the DRC and Guinea by DNDi in partnership with national authorities, which demonstrated that the drug is safe and effective. Existing treatments require a ten-day oral treatment regimen or a combination of injection and oral therapy that requires several days of hospitalization for patients in the most advanced stages. The DRC approval, which will make the drug available free of cost to patients in the country, is expected to be followed by endorsements in other endemic countries soon.A research team from the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health has shared promising early results from a first-in-human clinical trial comparing a new investigational vaccine against Lassa fever and rabies to a licensed rabies vaccine, finding that the vaccine candidate was safe and induced rapid and robust immune responses against both viruses. There are currently no available vaccines for Lassa fever, a dangerous disease considered a priority threat with epidemic and pandemic potential that is common in parts of Western and sub-Saharan Africa, which also have a high burden of another severe disease: rabies. A dual vaccine could help streamline health care delivery in settings with limited health care infrastructure; the vaccine candidate can also be freeze-dried for storage, making it well suited to low-resource settings where it can be difficult to maintain the cold chain. Last week, DNDi, the Medicines for Malaria Venture (MMV), and the Global Antibiotic Research and Development Partnership (GARDP) announced a new cooperative agreement to explore how the three organizations can work together to advance global health research and development (R&D) amid global aid cuts and calls to reshape the global health architecture. The organizations plan to pool their expertise and resources to advance the R&D of effective and affordable medicines, while centering patient needs and equity. In addition, the partners will collaborate on policy advocacy and communications activities to raise awareness of the impact and promise of the nonprofit product development partnership model in advancing innovative, lifesaving medicines for critical, but often overlooked, diseases.  

A Phase 1 clinical trial testing a candidate that could become the first vaccine for leishmaniasis, a disfiguring skin disease, is set to begin soon in Kenya and Brazil, where the disease in endemic, as well as in Cincinnati, Ohio, as the disease risk grows in the United States. The Global Health Innovative Technology (GHIT) Fund is supporting the trial, which will test the safety and immune response of the candidate in healthy people. The vaccine, which was developed using CRISPR gene-editing technology to mutate the parasite that causes the disease, previously demonstrated strong results in mice and has received US Food and Drug Administration approval as an investigational new drug, which allows the product to be tested in humans. The Coalition for Epidemic Preparedness Innovations (CEPI) has announced that it is providing funding to fast-track the development of three Ebola Bundibugyo virus vaccine candidates, as the concerning outbreak of the Bundibugyo strain, for which there are no approved vaccines, continues to grow in the Democratic Republic of the Congo and Uganda. Specifically, the funding will support preclinical development and Phase 1 clinical testing of Moderna’s mRNA vaccine candidate; help accomplish a key early step in vaccine manufacturing for IAVI’s vaccine, which is based on the organization’s rVSV vaccine platform; and help the University of Oxford prepare for a Phase 1 trial of its vaccine, which is based on the same platform as its Oxford/AstraZeneca COVID-19 vaccine.  Last week, Zendal announced the launch of the international MTBVAC AVANTE consortium to accelerate clinical development and prepare regulatory and policy pathways to ensure broad and equitable access of the MTBVAC tuberculosis (TB) vaccine candidate over the next four years. The current TB vaccine is more than 100 years old and offers inconsistent protection in adults against pulmonary TB, so a new and improved vaccine that is safe and effective across diverse populations who face TB risk will be essential to ending the pandemic. With funding from the Global Health EDCTP3, the consortium of 12 European and African partners will initially support two major ongoing trials in high-TB regions in sub-Saharan Africa, one evaluating the vaccine in adolescents and adults and one comparing the candidate’s protection in newborns to the existing vaccine.  

IAVI recently announced the start of a first-in-human clinical trial evaluating a combination injection of four broadly neutralizing antibodies, with the aim of eventually developing a tool to prevent HIV transmission in infants during the postnatal period. The combination shot includes four antibodies that target different HIV receptors, including IAVI’s broadly neutralizing antibody ePGT121v1-LS. The current trial is evaluating safety, dosing, pharmacokinetics, durability, and efficacy in 118 adult participants across the United States and Peru, and, if successful, could pave the way for future studies in infants. A research team has identified a bacterium strongly associated with noma, a potentially fatal infection for which the underlying cause is poorly understood. The researchers used metagenomic sequencing and machine learning algorithms to analyze saliva samples from children with acute noma. They identified a bacterial species that may be responsible for the disease, which was detected in the early stages of infection and does not carry known antibiotic resistance genes, suggesting that infection could be effectively treated with existing antibiotics if detected early enough. These findings also pave the way for the development of diagnostic tools that can detect noma early on, when treatment is most effective and before irreversible damage has been done. Last week, Butterfly Network shared that it received regulatory clearance from the US Food and Drug Administration for its artificial intelligence (AI)-powered ultrasound, offering a critical new tool to improve maternal care in low-resource settings with limited access to prenatal imaging. Compared to traditional ultrasounds that rely on expensive technology, the new device is more affordable and provides results in less than two minutes with fewer inputs. The tool has already been deployed in Malawi and Uganda, and this latest approval will enable its widespread rollout in the United States. 

Newly shared results from a Phase 3 clinical trial found that a single-dose dengue vaccine was highly effective at preventing severe dengue, as the mosquito-borne disease continues to spread into new areas around the world. The vaccine, developed by the Butantan Institute in Brazil, was recently approved in Brazil for use in people aged 12 to 49 years old. The new trial found that among thousands of participants aged 2 to 59 years old, the vaccine was effective at preventing symptomatic dengue but especially effective—80.5 percent— at preventing hospitalization for at least five years. The World Health Organization (WHO) has shared new guidance highlighting critical targets for new antibiotics, as the global threat of antimicrobial resistance (AMR) continues to grow and outpace the development of new and innovative antimicrobials. The three areas outlined are the development of new drugs to fight Gram-negative bacteria that cause serious infections that are especially difficult to fight; new drugs for patients with serious infections that can no longer be treated with vancomycin, a powerful last-resort antibiotic; and new treatments for bacterial meningitis, which is getting harder to treat due to growing antibiotic resistance. While the research and development of a new antibiotics can be difficult, expensive, and not as profitable as other products, WHO aims to highlight key areas for investors and developers to focus their efforts to grow the pipeline of new, urgently needed tools. Last week, the Sabin Vaccine Institute announced that it has completed enrollment in six Phase 2 clinical trials for its Marburg and Sudan Ebolavirus vaccines in Kenya, Uganda, and the United States, as increasing outbreaks of both viruses in recent years have highlighted the urgent need for vaccines. There are currently no licensed vaccines for protection against the highly contagious, life-threatening diseases caused by these viruses. The Marburg vaccine has also been evaluated during recent outbreaks in Rwanda in Ethiopia. Both candidates have so far demonstrated strong safety and efficacy profiles. The Sabin Vaccine Institute has also begun planning larger Phase 3 trials for each of the vaccines.